The aim of this study is to investigate the regulation of secretion of two digestive enzymes, lingual lipase and amylase, from serous (von Ebner's) glands of the tongue. These exocrine glands are the only known source of lingual lipase which is responsible for the first step in lipid digestion occurring in the stomach at acid pH. It hydrolyzes triacylglycerols to fatty acids and partial acylglycerols and is essential for proper functioning of pancreatic lipase. It is the major means of fat digestion in instances of pancreatic deficiency that occur in the premature or neonatal mammal in and pancreatic disease such as cystic fibrosis. Very little is known about enzyme release from lingual serous glands. Recent investigations showed that neurotransmitter stimulation of protein secretion from this minor salivary gland is similar to the pancreas being cholinergic in nature and different from the parotid, a major salivary gland. Hormonal or peptidergic stimulation of secretion with secretagogues that stimulate enzyme secretion by the parotid gland, the stomach, and the pancreas will be investigated in vitro by methods similar to those used for neurotransmitter simulators. Dose-response, kinetic, and developmental studies will be undertaken. Cholinergic stimulation in other tissues is usually accompanied by phosphatidyl-inositol turnover. Evidence of this turnover will be sought by incubating dissected lingual serous glands with 3H- inositol or 32P-phosphate and observing changes in labeling and content of phosphatidylinositol, phosphatidic acid, and polyinositol phosphates under the influence of carbachol. The possible role of diacylglycerols as a second messenger in protein secretion from exocrine glands by activating protein kinase C will be studied by in vitro stimulation of secretion of the two enzymes by phorbol esters or various diacylglycerols. Studies of protein kinase C and interactions with protein kinase A will identify the substrates of protein kinase C and A. The effects of sphingosine, a natural inhibitor of protein kinase C, on secretion stimulated by cholinergic agonists or a phorbol ester will be studied as well as the role of microtubules in stimulated secretion by inhibiting microtubule assembly. These investigations will characterize the regulation of protein secretion in lingual serous glands and will make possible further elucidation of the signal transduction mechanism. When the complete mechanism of secretion is known, it will be possible to use this knowledge to treat pancreatic deficiency diseases by stimulating secretion of lingual lipase.